The objective of the proposed investigation is to delineate the control mechanism involved in the regulation of avian oncornavirus gene expression, particularly those responsible for neoplastic transformation, as a means to ultimately elucidate the interactions of cellular and viral components required to initiate and maintain the transformed phenotype. These studies will be performed with a mammalian cell line (Microtus agrestis, field vole) transformed by an avian oncornavirus. One of the interesting features of transformed vole cells is their ability to revert to the normal cell phenotype. Studies to date indicate that revertant vole cells: (1) exhibit the growth properties of uninfected normal vole cells; (2) contain the entire biologically functional viral genome including the viral gene required for neoplastic transformation; and (3) express all of the viral genes including the transforming gene sequences as RNA at levels similar to transformed vole cells. Thus, the unique feature of the transformed/ revertant vole cell system is the presence of control mechanism(s) that appear to be responsible for the regulation of not only the viral structural genes but the viral transforming gene as well. Consequently, the identification of the lesion affecting the expression of the transforming genes in the revertant vole cells could provide information with respect to the cellular and viral interactions necessary for the expression of the transformed phenotype. Studies are proposed (1) to elucidate the level(s) of post-transcriptional control; (2) to identify the cellular and viral components involved; and (3) to determine the cellular location of the sarcoma gene product (60K protein) which might be indicative of the mechanism(s) of viral-induced oncogenesis and the site at which the sarcoma gene product acts. Included in these studies will be a rigorous analysis of the proviral integration site, the structural features of viral RNA (size, maturation, processing, etc.) and the detection, quantitation and structural analysis of viral proteins including the sarcoma gene product (60K protein) in both revertant and transformed vole cells.